Obesity to Type 2 Diabetes Mellitus: Importance of Longitudinal Characterization of the Progressive Phases as Identified in Rhesus Monkeys Maintained Under Constant Diet and Environmental Conditions

Abstract

The complex physiological mechanisms that underlie the links between obesity and T2DM involve “adiposity-induced” alterations in beta cell function —not yet mechanistically understood. Clearly the changes in beta cell function are greatly increased during the progression of obesity, --not reduced!! AND multiorgan insulin resistance whose mechanisms are unknown (although likely reduced by weight loss). Rhesus monkeys have shown these and have provided an amazing look at the Phases that lead to T2DM. We have previously summarized, in a table of 49 variables, the many ways that the nonhuman primate rhesus monkey offers exciting opportunities for insight into these extraordinary conditions compared to the human with T2DM. The Importance of longitudinal characterization, with a number of measurements that are regularly and periodically carried out to assess longitudinally some of the pathophysiological processes that develop spontaneously and naturally in these monkeys as they progress from normal, lean, young animals to obese animals with or without various physiological disturbances undergo the aging process. Usually these disturbances develop at varying rates in different monkeys and include hypertension, hyperlipidemia, hyperinsulinemia, hyperglycemia, impaired glucose tolerance, insulin resistance, peripheral neuropathy, impaired renal clearance, and cardiovascular disease—in short, the entire syndrome that becomes manifest in aged and diabetic humans. The longitudinal studies depend specifically on regular assessment of each animal and determination of the rate at which that animal is or is not progressing in the development of pathophysiological disturbances. Identification of phases allows one to estimate where a given monkey is in regard to the progression to overt diabetes. Application to humans will greatly increase our predictive ability to understand the mechanisms underlying both obesity and T2DM. NIA NO1AG3 1012. This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.